We found a potential new predisposing factor for HD, HLA DRB1*0415 allele, never described before as genetic background to insulin autoimmune syndrome in Caucasians.
Both cases are associated with HLA-DRB1*04:03 and confirm the evidence that HLA-DRB1*04:03 rather than HLA-DRB1*04:06 is specifically related to IAS susceptibility in Europeans.
These two Portuguese patients with IAS had different HLA-DR4 subtypes and insulin autoantibodies: DRB1*0406 and a polyclonal antibody in a patient treated with penicillin, and DRB1*0403 and a monoclonal antibody in a patient with "idiopathic" IAS.
The present report demonstrated the first Japanese patient with insulin autoimmune syndrome carrying HLA-DRB1*0401 who was revealed to have monoclonal insulin autoantibodies.
Because of such a strong HLA association in IAS, we performed intra- and interethnic studies on IAS-associated DRB1 alleles and searched for the critical amino acid residue(s) for IAS pathogenesis.